The Role of PIM Kinases in Pediatric Solid Tumors
Abstract
:Simple Summary
Abstract
1. Introduction
2. PIM Kinase Family
3. PIM Kinase Structure
4. PIM Kinases Expression and Regulation
5. Role of PIM Kinases in Carcinogenesis
5.1. Apoptosis
5.2. Cell Cycle
5.3. C-Myc Regulation
5.4. Motility
5.5. Cancer Cell Stemness
6. Role of PIM Kinases in Pediatric Malignancies
6.1. Hepatoblastoma
6.2. Neuroblastoma
6.3. Osteosarcoma
7. Pharmacologic Inhibition of PIM Kinases
7.1. Therapeutic Agents
7.2. Clinical Trials
7.3. Combination Therapies including PIM Kinase Inhibitors
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Pharmacologic Agent | Cancer Type or Condition | Clinical Trial Phases Conducted | Clinical Trial Number(s) |
---|---|---|---|
AZD1208 | Acute myelogenous leukemia | Phase I (Terminated) | NCT01489722 |
Advanced solid tumors, malignant lymphoma | Phase I (Completed) | NCT01588548 | |
PIM447 | Myelofibrosis | Phase I (Completed) | NCT02370706 |
Multiple myeloma | Phase I (Completed) | NCT02160951 | |
Relapsed and/or refractory multiple myeloma | Phase I (Completed) | NCT02144038 | |
Acute myeloid leukemia, high risk myelodysplastic syndrome | Phase I (Completed) | NCT02078609 | |
Relapsed and/or refractory multiple myeloma | Phase I (Completed) | NCT01456689 | |
SGI-1776 | Relapsed and/or refractory leukemias | Phase I (Withdrawn) | NCT01239108 |
Prostate cancer, Non-Hodgkin lymphoma | Phase I (Terminated) | NCT00848601 | |
INCB053914 | Relapsed and/or refractory multiple myeloma | Phase I (Withdrawn) | NCT04355039 |
Advanced solid tumors | Phase I/II (Terminated) | NCT02587598 | |
Relapsed and/or refractory diffuse large B cell lymphoma | Phase I (Completed) | NCT03688152 | |
CX-4945 | Cholangiocarcinoma | Phase I/II (Completed) | NCT02128282 |
Multiple myeloma | Phase I (Unknown) | NCT01199718 | |
Advanced solid tumors, breast cancer, inflammatory breast cancer, Castleman disease, multiple myeloma | Phase I (Unknown) | NCT00891280 | |
SEL24/MEN1703 | Acute myeloid leukemia | Phase I/II (Recruiting) | NCT03008187 |
LY-2835219 (Abemaciclib) | Relapsed or refractory pediatric solid tumors | Phase I (Recruiting) | NCT04238819, NCT02644460 |
Pediatric brain tumors | Phase I (Recruiting) | NCT02644460 | |
Advanced malignancies | Phase I (Active, Completed) | NCT02117648, NCT01394016, NCT02919696, NCT04071262, NCT02857270, NCT01655225, NCT05307705, NCT02791334, NCT02745769 | |
Breast cancer, metastatic breast cancer | Phase I (Active, Completed), Phase II (Active, Completed, Recruiting), Phase III (Active, Completed, Recruiting), Phase IV (Recruiting, Terminated, Withdrawn) | NCT02831530, NCT02441946, NCT02246621, NCT02102490, NCT05169567, NCT02763566, NCT04752332, NCT03988114, NCT02057133, NCT03703466, NCT03763604, NCT02779751, NCT02675231, NCT02792725, NCT03155997, NCT02747004, NCT04031885, NCT02107703, NCT03130439, NCT04707196, NCT05169567, NCT04975308, NCT04188548, NCT02784795, NCT02688088, NCT04305834, NCT03979508, NCT05307705, NCT04481113, NCT04351230, NCT04256941, NCT03878524 | |
Non-small cell lung cancer, metastatic non-small cell lung cancer | Phase I (Active, Completed), Phase II (Completed), Phase III (Active) | NCT02079636, NCT02450539, NCT02779751, NCT02152631, NCT02411591 | |
Sarcoma, dedifferentiated liposarcoma | Phase II (Active), Phase III (Recruiting) | NCT02846987, NCT04967521 | |
Brain tumor, recurrent glioblastoma | Phase II (Active, Withdrawn) | NCT03220646, NCT02981940, NCT04118036 | |
Metastatic castration-resistant prostate cancer | Phase II (Active, Recruiting), Phase III (Recruiting) | NCT04408924, NCT03706365, NCT05288166 | |
Mantle cell lymphoma | Phase II (Active) | NCT01739309 | |
Pancreatic ductal adenocarcinoma | Phase II (Completed) | NCT02981342 | |
Metastatic breast or non-small cell lung cancer, or melanoma with brain metastasis | Phase II (Completed, Withdrawn) | NCT02308020, NCT04585724 | |
Small cell lung cancer | Phase I (Recruiting) | NCT04010357 | |
Metastatic cancer, BRAF V600E, MEK1, MEK2, ERK, KRAS, or RAF1 gene mutations | Phase II (Recruiting) | NCT04534283 | |
Endometrial cancer, metastatic endometrial cancer | Phase I (Recruiting), Phase II (Active) | NCT04188548, NCT04049227, NCT04469764 | |
Metastatic or locally advanced anaplastic/undifferentiated thyroid cancer | Phase II (Recruiting) | NCT04552769 | |
Unresectable of metastatic colorectal cancer | Phase I/II (Recruiting) | NCT04616183 | |
Mesothelioma | Phase II (Recruiting) | NCT03654833 | |
Multiple myeloma | Phase I/II (Recruiting) | NCT03732703 |
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Julson, J.R.; Marayati, R.; Beierle, E.A.; Stafman, L.L. The Role of PIM Kinases in Pediatric Solid Tumors. Cancers 2022, 14, 3565. https://doi.org/10.3390/cancers14153565
Julson JR, Marayati R, Beierle EA, Stafman LL. The Role of PIM Kinases in Pediatric Solid Tumors. Cancers. 2022; 14(15):3565. https://doi.org/10.3390/cancers14153565
Chicago/Turabian StyleJulson, Janet Rae, Raoud Marayati, Elizabeth Ann Beierle, and Laura Lee Stafman. 2022. "The Role of PIM Kinases in Pediatric Solid Tumors" Cancers 14, no. 15: 3565. https://doi.org/10.3390/cancers14153565